The present invention relates to stabilized solid state pharmaceutical compositions containing an active component selected from pharmaceutically active derivatives of vitamin D.sub.2 and vitamin D.sub.3.
Derivatives of vitamin D.sub.2 and vitamin D.sub.3, which generally possess at least the activity of their underivatized precursors, have been found to be useful in medicine, e.g. they increase the serum calcium level, inhibit parathyroid hormone, and affect bone formation: they may also inhibit the proliferation of psoriatic and certain cancer cells. In particular, they are used to treat symptoms such as chronic renal failure, hypoparathyroidism, vitamin-D-resistant rickets, osteomalacia, osteoporosis and psoriasis.
However, such derivatives have the disadvantage of low stability under ordinary storage conditions. Moreover, refrigeration, protection against actinic radiation and replacement of the ambient atmosphere have not been found to be satisfactory as a means of stabilization and are often costly. Consequently, various stabilization methods have been proposed. Thus, by way of example, EP 413828A teaches dispersion of active ingredient in an excipient readily soluble in organic solvent and a basic substance, EP 387808A uses a stabilizer selected from polyvinylacetal diethylaminoacetate and hydroxypropylcellulose, while JP 258722/91 discloses compositions containing crystalline cellulose and butylated hydroxytoluene (BHT) or butylated hydroxyanisole (BHA), as antioxidant. JP 074123/92 discloses compositions containing active forms of vitamin D.sub.3 and gelatin in the same phase; in an example of a liquid phase composition, a polyoxyethylene hardened castor oil derivative was also present.
All of these exemplary solid pharmaceutical compositions show unsatisfactory stability at elevated temperatures or/and humidities. Consequently, there is a great need for improved stabilized solid state pharmaceutical compositions containing the ingredients referred to above.
Accordingly, it is an object of the invention to provide solid pharmaceutical compositions containing an active component selected from pharmaceutically active derivatives of vitamin D.sub.2 and vitamin D.sub.3, which exhibit improved stability for a prolonged period of time. Other objects of the invention will appear from the description which follows.